Alexander M. Kaizer

The Intervention Probability Curve: Modeling the Practical Application of Threshold-Guided Decision-Making, Evaluated in Lung, Prostate, and Ovarian Cancers

Abstract Background: Diagnostic prediction models are useful guides when considering lesions suspicious for cancer, as they provide a quantitative estimate of the probability that a lesion is malignant. However, the decision to intervene ultimately rests on patient and physician preferences. The appropriate intervention in many clinical situations is typically defined by clinically relevant, actionable subgroups based upon the probability of malignancy. However, the “all-or-nothing” approach of threshold-based decisions is in practice incorrect. Methods: Here, we present a novel approach to understanding clinical decision-making, the intervention probability curve (IPC). The IPC models the likelihood that an intervention will be chosen as a continuous function of the probability of disease. We propose the cumulative distribution function as a suitable model. The IPC is explored using the National Lung Screening Trial and the Prostate Lung Colorectal and Ovarian Screening Trial datasets. Results: Fitting the IPC results in a continuous curve as a function of pretest probability of cancer with high correlation (R2 > 0.97 for each) with fitted parameters closely aligned with professional society guidelines. Conclusions: The IPC allows analysis of intervention decisions in a continuous, rather than threshold-based, approach to further understand the role of biomarkers and risk models in clinical practice. Impact: We propose that consideration of IPCs will yield significant insights into the practical relevance of threshold-based management strategies and could provide a novel method to estimate the actual clinical utility of novel biomarkers.